Radioiodinated progesterone derivative for progesterone receptor targeting with enhanced nucleus uptake via phenylboronic acid conjugation

Abstract

A novel 131I‐radiolabeled probe with aromatic boronate motif (131I‐EIPBA) was designed to target progesterone receptor (PR)–positive breast cancer with enhanced nucleus uptake. Acetylene progesterone was conjugated with pegylated phenylboronic acid via click reaction and radiolabeled with 131I to afford 131I‐EIPBA. Meanwhile, 131I‐EIPB without boronate was prepared as control agent. After determination of the lipophilicity and stability of these tracers, in vitro cell uptake studies and in vivo biodistribution in rats were performed to verify the enhanced nucleus uptake and PR targeting ability of 131I‐EIPBA. 131I‐EIPBA was obtained with moderate radiochemical yield (40.35 ± 3.52%) and high radiochemical purity (>98%). As expected, the high binding affinity (39.58 nM) of 131I‐EIPBA for PR was determined by cell binding assay. The internalization ratio of 131I‐EIPBA was remarkably higher than that of 131I‐EIPB in PR‐positive MCF‐7 cells. Furthermore, the enhanced nucleus uptake of 131I‐EIPBA (0.59 ± 0.02%) was found to be significantly higher than that of 131I‐EIPB (0.13 ± 0.01%) in MCF‐7 cells. A novel 131I‐EIPBA compound was developed for PR targeting with improved cellular nucleus uptake. Furthermore, the introduction of aromatic boronate motif provides a worthwhile strategy for enhancing the nuclear receptor targeting of tracers.

Preclinical Evaluation of a Novel 99mTc-Labeled CB86 for Rheumatoid Arthritis Imaging

“…The radiolabeling method of DTPA-CB86 was performed as described in our previous methods. 20 Under radio-HPLC, 99m Tc-DTPA-CB86 showed a retention time of 25.7 min. The radiolabeling efficiency, radiochemical purity, and specific activity of 99m Tc-DTPA-CB86 were 95.86 ± 2.45%, 97.45 ± 0.69%, and 2.6 MBq/nmol, respectively.…”

“…The radiolabeling method of DTPA-CB86 was performed as described in our previous methods . Under radio-HPLC, 99m Tc-DTPA-CB86 showed a retention time of 25.7 min.…”

“…In vitro stabilities in phosphate-buffered saline (PBS, pH=7.4) or mouse serum were determined similarly to our previously described procedures with minor modifications …”

“…Cell uptake, blocking, and efflux assays were performed as previously described with minor modifications . Briefly, the RAW264.7 cell lines were cultured in DMEM supplemented with 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin.…”

5-Iodo-1H-1,2,3-triazoles as Versatile Building Blocks

“…36 Several publications are focused on the synthesis and properties of 5-iodotriazoles through Route B without further C-I functionalization. [37][38][39][40][41][42][43] It is particularly remarkable that synthetic approach B makes radiolabeled 5-iodo-1,2,3-triazoles easily accessible if [ 125 I]NaI 44 or [ 131 I]NaI 45 is employed as the iodine source. Route C is similar to B, and differs only in the iodine source: excess CuI is used both as catalyst and as an iodinating agent.…”